Both the Massachusetts Department of Environmental Protection MADEP and the Total Petroleum Hydrocarbon Criteria Working Group TPHCWG developed fraction-based approaches for assessing human health risks posed by total petroleum hydrocarbon TPH mixtures in the environment. Both organizations defined TPH fractions based on their expected environmental fate and by analytical chemical methods. They derived toxicity values for selected compounds within each fraction and used these as surrogates to assess hazard or risk of exposure to the whole fractions. Membership in a TPH fraction is generally defined by the number of carbon atoms in a compound and by a compound-s equivalent carbon EC number index, which can predict its environmental fate. Here, we systematically and objectively re-evaluate the assignment of TPH to specific fractions using comparative molecular field analysis and hierarchical clustering. The approach is transparent and reproducible, reducing inherent reliance on judgment when toxicity information is limited. Our evaluation of membership in these fractions is highly consistent ̃80% on average across various fractions with the empirical approach of MADEP and TPHCWG. Furthermore, the results support the general methodology of mixture risk assessment to assess both cancer and noncancer risk values after the application of fractionation.